Ketamine in Adolescents With Treatment-Resistant Depression
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|ClinicalTrials.gov Identifier: NCT02078817|
Recruitment Status : Completed
First Posted : March 5, 2014
Results First Posted : January 27, 2020
Last Update Posted : January 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder||Drug: Ketamine||Phase 2|
Depression frequently emerges during adolescence and is associated with severe outcomes. Current interventions do not lead to remission for many adolescents. Treatment-resistant depression (TRD) in adolescence is an ominous prognostic indicator for a lifetime of suffering and increased risk for suicide. Efforts should be directed toward novel interventions that could alter this perilous course. Theoretically, restoration of healthy development during this critical window would substantially improve outcomes over the lifespan.
Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor that has long been used for induction and maintenance of anesthesia in children and adults, and recently has been investigated for its rapid antidepressant effects. Randomized, double-blind, saline-controlled trials in adults with TRD have demonstrated that a single, subanesthetic infusion of intravenous (IV) ketamine at 0.5 mg/kg over 40 minutes can produce a rapid (within 2 hours) antidepressant response (Ibrahim et al., 2011; Zarate et al., 2006). Recent evidence suggests that serial doses of ketamine may be even more effective and may lead to more prolonged remission (aan het Rot et al., 2010; Murrough et al., 2012). Our current research at using serial dosing of IV ketamine among adult veterans with TRD over a 2-week period has shown promising results, with a response rate of 92% among the 12 participants to date.
No results from any studies examining effectiveness of either single-dose or serial-dose ketamine have yet been published in adolescents with TRD. Because of the ongoing neurodevelopment in adolescence, which is thought to confer enhanced neuroplasticity, it is possible that adolescents with TRD could show greater responses and more sustained remission than adults with TRD. The biological mechanisms of depression impacted by ketamine are only now being uncovered in adults (Zarate et al., 2013). Characterization of the neural mechanisms underlying ketamine response or non-response in adolescents with TRD will represent a significant advance. The specific aims of this preliminary study are as follows:
Aim #1: To determine the efficacy of repeated-dose subanesthetic IV ketamine among adolescent patients with TRD.
Hypothesis: Based on previous results in adults with TRD, we predict that response rates will improve over the course of six treatments of ketamine.
Aim #2: To explore durability of antidepressant response to repeated dose of IV ketamine in a 4-week observational period.
Hypothesis: Based on the inherent neuroplasticity in adolescence due to ongoing neurodevelopment, adolescents may show a more durable clinical response than has been seen in adults.
Aim #3: To study the neurobiological mechanisms of response to ketamine. We will examine relevant biological systems using several different brain imaging indices and measures of intracellular functioning from peripheral blood.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open-Label Intravenous Subanesthetic Ketamine for Adolescents With Treatment-Resistant Depression|
|Study Start Date :||September 2014|
|Actual Primary Completion Date :||March 2018|
|Actual Study Completion Date :||March 2018|
Intravenous ketamine 0.5 mg/kg over 40 minutes will be given 6 times over 2 weeks.
IV infusions of 0.5mg/kg of Ketamine hydrochloride over a 40-minute infusion period. Participants will receive a total of 6 doses over a 2-week period.
- Number of Responders Measured by Clinical Global Impression (CGI) [ Time Frame: 2 weeks ]Responders will be defined as those with CGI ratings (given by the study clinician) of 1 or 2 (much or very much improved). Patients that are given a scores of 3-7 (minimally improved to very much worse) will be considered non-responders.
- Children's Depression Rating Scale-Revised [ Time Frame: 2 weeks ]The CDRS-R measure is given in interview form to child and parent separately. A consensus is then created with best-estimate for 17 items (each with a range of 1-5 or 1-7) using both sources of information. The total score is the sum of 17 item scores, ranging from 17-113 with higher scores indicating greater depression symptoms.
- Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 2 weeks ]MADRS is a 10-item clinician-administered inventory measuring depression symptoms. Items are scored on a scare from 0 (none) to 6 (constant). Total scores are a sum of the 10 item scores, ranging from 0 to 60, with higher scores indicating greater symptom severity.
- Beck Depression Inventory-II (BDI-II) [ Time Frame: 2 weeks ]BDI-II is a 21-item self-report multiple-choice inventory that assesses the severity of depressive symptoms over the prior week. Items are rated on a 4-point scale ranging from 0 to 3. Total scores are a sum of the 21 item scores ranging from 0 to 63. Higher scores indicate more severe depression symptoms.
- Change in Clinician Administered Dissociative States Scale (CADSS) [ Time Frame: baseline, 2 weeks ]CADSS is a 27-item instrument measuring symptoms of dissociative stress, with 19 items completed by the patient and 8 items completed by the clinician. Items are rated on a scale of 0 (not at all) to 4 (extreme). Total scores are a sum of the 27 item scores and range from 0 to 108, with higher scores indicating greater symptom severity.
- Maximum Change in Systolic Blood Pressure [ Time Frame: 2 hours and 40 minutes ]Vital signs were measured every 15 minutes, starting from the beginning of the infusion and ending 2 hours after the infusion ended (2 hours, 40 minutes total). Maximum increase of blood pressure compared to baseline was calculated.
- Maximum Change in Diastolic Blood Pressure [ Time Frame: baseline, 45 minutes post infusion ]
- Maximum Change in Heart Rate [ Time Frame: 4 hours ]
- Maximum Decrease in Pulse Oximetry [ Time Frame: 4 hours ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02078817
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55454|